title: Structure of nicotinic acid mononucleotide adenylyltransferase from Bacillus anthracis.
abstract: Nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC 2.7.7.18) is the penultimate enzyme in the biosynthesis of NAD(+) and catalyzes the adenylation of nicotinic acid mononucleotide (NaMN) by ATP to form nicotinic acid adenine dinucleotide (NaAD). This enzyme is regarded as a suitable candidate for antibacterial drug development; as such, Bacillus anthracis NaMNAT (BA NaMNAT) was heterologously expressed in Escherichia coli for the purpose of inhibitor discovery and crystallography. The crystal structure of BA NaMNAT was determined by molecular replacement, revealing two dimers per asymmetric unit, and was refined to an R factor and R(free) of 0.228 and 0.263, respectively, at 2.3 A resolution. The structure is very similar to that of B. subtilis NaMNAT (BS NaMNAT), which is also a dimer, and another independently solved structure of BA NaMNAT recently released from the PDB along with two ligated forms. Comparison of these and other less related bacterial NaMNAT structures support the presence of considerable conformational heterogeneity and flexibility in three loops surrounding the substrate-binding area.
authors.affiliation: Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, Alabama 35294-4400, USA.
authors.forename: Shanyun
authors.initials: S
authors.lastname: Lu
authors.forename: Craig D
authors.initials: CD
authors.lastname: Smith
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Yang
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Pruett
authors.forename: Lisa
authors.initials: L
authors.lastname: Nagy
authors.forename: Deborah
authors.initials: D
authors.lastname: McCombs
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Delucas
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Brouillette
authors.forename: Christie G
authors.initials: CG
authors.lastname: Brouillette
mesh_terms: D000595:Amino Acid Sequence; D001408:Bacillus anthracis / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D017124:Conserved Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000096:biosynthesis; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D009243:NAD; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C038480:nicotinic acid mononucleotide adenylyltransferase